The subject invention relates to novel heterocyclic derivatives that selectively bind to the dopamine D3 receptor. The therapeutic effects of currently available antipsychotic agents (neuroleptics) are generally believed to be exerted via blockade of D2 receptors; however this mechanism is also thought to be responsible for undesireable extrapyramidal side effects (eps) associated with many neuroleptic agents. Without wishing to be bound by theory, it has been suggested that blockade of the dopamine D3 receptor may give rise to beneficial antipsychotic activity without significant eps. (see for example Sokoloff et al, Nature, 1990; 347:146-151; and Schwartz et al, Clinical Neuropharmacology, Vol 16, No. 4, 295-314, 1993). This receptor is found in high abundance in brain regions associated with emotional and cognitive functions. Compounds that selectively bind to the dopamine D3 receptor are useful in treating certain central nervous system disorders. These central nervous system disorders include the following indications:    1) Psychoses (including schizophrenia)—See, for example, Biochem Pharmacol, 1992, 3(4), 659-66; Clin Neuropharmacol, 1993, 16(4), 295-314; Neuropsychopharmacology, 1997, 16(6), 375-84; Am J Psychiatry, 1999, 156(4), 610-61 6; Psychopharmacology (Berl), 1995, 120(1), 67-74.    2) Substance dependence and substance abuse—See, for example, Neuroreport, 1997, 8(9-10), 2373-2377; J Pharmacol Exp Ther, 1996, 278(3), 1128-37; Brain Hes Mol Brain Res, 1997, 45(2),335-9.    3) Mood Disorders (including mania, depressive disorders and bipolar disorders)—See, for example, Clin Neuropharmacol, 1998, 21 (3), 176-80; Am J Med Genet, 1998, 81 (2), 192-4; J Clin Psychiatry, 1995, 56(11), 514-518; J Clin Psychiatry, 1995, 56(9), 423-429; Am J Med Genet,1995, 60(3), 234-237; Pharmacopsychiatry, 1999, 32(4), 127-135; J Affect Disord, 1999, 52(1-3), 275-290; Am J Psychiatry, 1999, 156(4), 610-616.    4) dyskinetic disorders (including Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia and Gilles de la Tourette Syndrome)—See, for example, Clin Neuropharmacol, 2000, 23(1), 34-44; EurJ Pharmacol, 1999, 385(1), 39-46.    5) sleep disorders (including narcolepsy)—The D3 agonist pramipexole causes narcolepsy. A D3 antagonist would be useful for reversing this undesireable side effect. See Aust Fam Physician, 1999, 28(7), 737; Neurology, 1999, 52(9), 1908-1910.    6) anxiety disorders (including obsessive compulsive disorders)—See, for example, Physiol Behav, 1997, 63(1), 137-141; J Clin Psychiatry, 1995, 56(9), 423-429; J Psychiatry Neurosci, 2000, 25(2), 185; J Affect Disord, 1999, 56(2-3), 219-226.    7) nausea—Dopamine antagonists are used alone and in combination with 5HT3 antagonists. See, for example, Support Care Cancer, 1998, 6(1), 8-12; Support Care Cancer, 2000, 8(3), 233-237; Eur J Anaesthesiol, 1999, 16(5), 304-307.    8) dementia—See, for example, Behav Brain Res, 2000, 109(1), 99-111; Neuroscience, 1999, 89(3), 743-749.
D3 receptor ligand compounds are also useful for the treatment of renal dysfunction. See WO 200067847.
Certain compounds within the scope of the present invention are generically disclosed and claimed in U.S. Pat. No. 5,801,176, the entire disclosure of which is herein incorporated by reference. For example, certain 6-trifluoromethyl benzo[b[thiophenes were disclosed therein to be useful as antipsychotics.